Older adults have excessively higher risk for mortality, reinfarction, stroke and heart failure (HF) after acute myocardial infarction (AMI). ACE inhibitors are one of the recommended preventive therapies after AMI. In our previous study, however, we found that 44% of elderly AMI patients were prescribed ACE inhibitors at doses lower than the doses with proven benefits in randomized-clinical-trial (RCTs). Part of this problem may be attributed to the lack of knowledge and clinical uncertainty on the treatment effectiveness and safety in the elderly since the elderly are insufficiently represented in the RCTs. If lower doses of ACE inhibitors have significant less benefit than the doses proven in RCTs, hundreds of thousands elderly AMI patients with lower doses may be put at a higher risk for death, re-infarction, stroke, and heart failure. However, if lower doses of ACE inhibitors have similar benefits and lower risk of adverse side effects such as hyperkalemia and acute renal failure, lower doses may be preferred in the elderly to avoid higher risk of severe adverse side effects. This retrospective observational cohort study will compare the real-world treatment effectiveness and safety of the established RCT doses of ACE inhibitors post AMI versus lower doses in the elderly. We will assemble a nationwide cohort of 80,000 elderly patients who were discharged with AMI and had ACE inhibitors usage in 2008 and 2009 using the research files from the newly available Medicare Chronic Condition Data Warehouse (CCW) and prescription Part D files. We will use cutting-edge innovative analytical methods such as multiple propensity scores and instrumental variables to address the research question. Our specific aims are 1) to investigate whether low and medium doses of ACE inhibitors have the same clinical benefit as the RCT doses in the prevention of recurrent AMI, stroke, heart failure requiring hospitalization, all-cause mortality, and composite of all end points in the elderly; 2) to investigate whether low and medium doses of ACE inhibitors have the same severe adverse side effects risk of a composite of acute renal failure and hyperkalemia requiring hospitalization and treatment discontinuation as the RCT doses in the elderly; and 3) investigate whether low and medium doses of ACE inhibitors have the same clinical benefit and risk as the RCT doses by age groups (65-74, 75-84, 85+) in the elderly. The lack of real-world treatment effectiveness and safety knowledge in the elderly may hinder hundreds of thousands elderly patients to be treated with therapies that optimally balance benefits and harms. Our long- term goal is to investigate real-world treatment effects among elderly patients with cutting-edge methods, which will complement RCT results, better inform clinical practice, and enhance the development of clinical guidelines and public health policies.